Lyme disease is caused by infection with a spirochete, Borrelia burgdorferi which is transmitted by the bite of Ixodes ticks. It is characterized by an annular skin lesion, usually starting at the site of tick attachment, known as erythema chronicum migrans (ECM) and, in decreasing order of frequency, by arthritis usually of the large joints, neurological and cardiac complications. The pathogenic relationships between infection with the Lyme disease spirochete and the development of lesions in the skin, heart, brain and joints are just beginning to be understood. Although the disease has many symptoms and may become chronic, very few spirochetes are found in Lyme disease patients. The hypothesis that the pathogenesis of this disease results from biological amplification of the effects of small numbers of organisms through the release of highly active spirochetal products or from the production of endogenous mediators of tissue injury, or both, will be investigated. In the present studies pathogenic components of B. burgdorferi will be examined. In so doing a more general understanding of bacterial pathogenesis and especially of bacteria-induced arthritis should result. Bacterial lipopolysaccharides (LPS) and peptidoglycans (PG) from the cell wall have been shown to mediate tissue damage. B. burgdorferi LPS and PG will be extracted and characterized with respect to their physicochemical, immunological and biological properties. Sugar and lipid moieties of the LPS will be identified as will the amino acid composition of the PG. LPS from cultured and freshly isolated spirochetes will be compared. Antibodies specific for LPS and PG will be used to neutralize the biological activities of these molecules. Monoclonal anti-LPS antibodies will be used to identify the epitopes responsible for the inflammatory actions of LPS and to locate the LPS using immunogold labeling and electron microscopy. Inflammatory lesions produced in animal skins following injection of PG or LPS will be characterized with respect to morphology and induction of endogenous mediators of inflammation. A rat model of Lyme arthritis will be investigated for the roles of LPS and PG in arthritogenesis.